预后相关的NAP1L4在肝细胞癌促癌机制和肿瘤免疫中的功能研究  

Study on the prognostic role of NAP1L4 in hepatocellular carcinoma: its oncogenic mechanisms and functions in tumor immunity

作　　者：孙佳[1] 谢昕 刘俊闪 SUN Jia;XIE Xin;LIU Junshan(Department of Oncology and Hematology,Children′s Hospital Affiliated of Zhengzhou University,He′nan Children′s Hospital Zhengzhou Children′s Hospital,He′nan Key Laboratory of Pediatric Hematology,Zhengzhou 450018,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院郑州儿童医院血液肿瘤科,河南省小儿血液医学重点实验室,河南郑州450018

出　　处：《胃肠病学和肝病学杂志》2024年第12期1669-1677,共9页Chinese Journal of Gastroenterology and Hepatology

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20220718)。

摘　　要：目的利用生物信息学方法和基础实验分析验证NAP1L4在肝细胞癌(hepatocellular carcinoma,HCC)中的表达模式、预后价值、分子机制、促癌作用和肿瘤免疫中的生物学功能。方法收集多个数据库信息,采取差异性分析和配对分析检测NAP1L4的表达水平,利用KM生存分析、单多因素Cox回归分析探讨NAP1L4对HCC预后的影响,利用GO分析、KEGG分析、GSEA分析、PPI网络和分子对接挖掘NAP1L4潜在分子机制,利用多种基础实验方法验证NAP1L4对HCC的促癌作用,利用单细胞聚类分析检测NAP1L4与肿瘤免疫细胞之间的关联。结果NAP1L4在HCC中表达水平显著升高,并伴随着生存期缩短,可以作为HCC不良预后的独立危险因素。NAP1L4参与调控组蛋白修饰、RNA加工和处理、泛素蛋白酶体系统等生物学过程,并与多种癌症相关蛋白相互作用,调控细胞周期、Wnt信号通路、Notch信号通路、VEGF信号通路等多种癌症相关通路。敲低NAP1L4的表达可以显著抑制肝癌细胞的增殖和迁移能力。NAP1L4在肝癌免疫微环境中主要表达于增殖性T细胞和免疫抑制性细胞Treg和CD8Tex。结论NAP1L4作为明确的促癌基因,不仅能作为HCC的确切诊断指标,还可以为精准治疗和免疫治疗提供一个可靠的联合作用靶点。Objective To utilize bioinformatics methods and basic experimental analysis to verify the expression patterns,prognostic value,molecular mechanisms,oncogenic roles and biological functions in tumor immunity of NAP1L4 in hepatocellular carcinoma(HCC).Methods Information from multiple databases was collected.Differential and paired analyses were performed to detect the expression levels of NAP1L4.KM survival analysis,univariate and multivariate Cox regression analyses were used to explore the impact of NAP1L4 on HCC prognosis.GO analysis,KEGG analysis,GSEA analysis,PPI network and molecular docking were employed to uncover the potential molecular mechanisms of NAP1L4.Various basic experimental methods were used to validate the oncogenic effects of NAP1L4 on HCC,and single-cell clustering analysis was used to examine the association between NAP1L4 and tumor immune cells.Results NAP1L4 was significantly upregulated in HCC,accompanied by a shortened survival period,and can serve as an independent risk factor for poor prognosis in HCC.NAP1L4 was involved in regulating biological processes such as histone modification,RNA processing and the ubiquitin-proteasome system,and interacted with various cancer-related proteins to regulate multiple cancer-related pathways,including cell cycle,Wnt signaling pathway,Notch signaling pathway and VEGF signaling pathway.The inhibition of NAP1L4 expression can significantly suppress the proliferation and migration capabilities of liver cancer cells.NAP1L4 was primarily expressed in proliferative T cells and immunosuppressive cells such as Tregs and CD8Tex in the liver cancer immune microenvironment.Conclusion NAP1L4,as a definitive oncogene,can not only serve as an accurate diagnostic marker for HCC but also provide a reliable combined therapeutic target for precision treatment and immunotherapy.

关 键 词：肝细胞癌 NAP1L4 生物信息学 分子机制 免疫治疗 

分 类 号：R735.7[医药卫生—肿瘤]